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Role of the Interleukin-1 Receptor Antagonist Gene Polymorphism (IL-1RN*2) in Early Gastric Cancer

Medical Oncology, Hospital of Urbino, Urbino, Italy

Annamaria Ruzzo

Institute of Biochemistry "G Fornaini", University of Urbino, Urbino, Italy

To the Editor:

We read with interest the recently published study by Glas et al¹ on the correlation between a variable number of tandem repeats polymorphism in the interleukin-1–receptor antagonist gene (IL-1RN*2) and early gastric cancer. In our opinion, a number of observations are worth mentioning.

In gastric cancer cases, Glas et al¹ found higher frequency of the homozygous IL-1RN2/2 genotype (58%) than that observed in previous studies in white populations (10% to 20%).^2-5 In general, the studied population of gastric cancer cases (Table 2 of their article)¹ showed an excess of IL-1RN homozygous frequencies (IL-1RN2/2 = 58 of 88; IL-1RN1/2 = 9 of 88; IL-1RN1/1 = 31 of 88). The authors did not discuss this relevant issue and they did not indicate how they identified and selected the 88 early gastric cancer cases. Another important piece of information that is missing is the analysis of linkage disequilibrium between the close IL-1B and IL-1RN loci. This is considered a relevant assessment in genetic studies and it estimates when specific variants are inherited together nonrandomly and more often than expected.⁶ In previous studies,^2-5 linkage disequilibrium between IL-1B-511, IL-1B-31, and IL-1RN loci was observed. Among the studied polymorphisms by Glas et al,¹ IL-1RN2/2 was the only one that showed correlation with early gastric cancer and this finding suggests an absence of strong linkage disequilibrium between IL-1RN and IL-1B loci.

To test their hypothesis, the authors compared genotypes of 88 early gastric cancer cases with genotypes of 145 controls. In our opinion, results would have been more robust if the authors had performed an overall analysis of consecutive gastric carcinomas including all stages of the disease, and then compared cases with early disease with cases with advanced-stage disease and compared cases with controls. Some additional concerns arise from the characteristics of the controls. The authors stated that the controls were matched blood donors, but it is unclear how matching was performed considering the different number of cases and controls, the unknown status of Helicobacter pylori infection in controls (H pylori positivity in the 88% of gastric cancer cases), and the marked difference in mean age between cases (65 years) and controls (45 years).

In summary, we appreciate the study by Glas et al, but additional information would help the readers to evaluate their results.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Glas J, Torok HP, Schneider A, et al: Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer. J Clin Oncol 22:4746-4752, 2004[Abstract/Free Full Text]

2. El-Omar EM, Carrington M, Chow WH, et al: Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398-402, 2000[CrossRef][Medline]

3. Machado JC, Pharoah P, Sousa S, et al: Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 121:823-829, 2001[CrossRef][Medline]

4. Figueiredo C, Machado JC, Pharoah P, et al: Helicobacter pylori and interleukin 1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94:1680-1687, 2002[Abstract/Free Full Text]

5. Graziano F, Ruzzo A, Santini D, et al: Prognostic role of Interleukin-1beta gene (IL-1B) and Interleukin-1 receptor antagonist gene (IL-1RN) polymorphisms in patients with advanced gastric cancer. J Clin Oncol 23:2339-2345, 2005[Abstract/Free Full Text]

6. Ardlie KG, Kruglyak L, Seielstad M: Patterns of linkage disequilibrium in the human genome. Nat Rev Genet 3:299-309, 2002[CrossRef][Medline]

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• In Reply:
  Jürgen Glas, Helga-Paula Török, Christian Folwaczny, Agnes Schneider, Manfred Stolte, Günter Brünnler, Ekehard D. Albert, and Reinhard Kopp
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